کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1370227 | 981814 | 2011 | 6 صفحه PDF | دانلود رایگان |
The aminomethylpyrimidines were investigated as a novel class of DPP-IV inhibitors. In this Letter, the binding mechanisms of how slight change of substitution or position influences the binding affinity of five representative analogs was investigated by molecular dynamics simulation, free energy calculations and energy decomposition analysis. The conserved hydrogen bonds with Glu205 and Glu206 slightly favor the inhibitor binding; the van der Waals interactions, especially the two key contacts with Tyr547 and Tyr666, dominate in the binding free energy and play a crucial role on distinguishing the high active inhibitors from the low ones.
The binding mechanisms of five representative aminomethylpyrimidine inhibitors of DPP-IV are elucidated through molecular dynamics simulations and MM/GBSA methods.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 21, Issue 22, 15 November 2011, Pages 6630–6635